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Cellular glycosylation facilitates molecular recognition of cells and biomolecules. A two-step N-glycan editing method enables selective glycoform ‘deletion’ and ‘insertion’ of new glycans, which can be used to probe their biological functions.
Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several nucleoside antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
A highly selective covalent peptide inhibitor of the peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is used to show that Pin1 cooperates with mutant KRAS to promote pancreatic ductal adenocarcinoma (PDAC) transformation.
Comprehensive informatic, structural and biochemical characterization of the GH128 family defines subgroups of glycoside hydrolase enzymes with unique recognition and cleavage mechanisms for 1,3-beta-glucan polysaccharide substrates.
Prostaglandins PGE1 and PGA1 have neuroprotective effects by enhancing the transcriptional activity of Nurr1 by directly binding to its ligand-binding domain and upregulating their target genes implicated in Parkinson’s disease.
Imaging studies revealed that m6A-binding YTHDF proteins promoted phase separation of core proteins of stress granules by reducing the critical size and activation energy barrier, thus promoting the formation of stress granules in cells.
Engineering of yeast transcription factors and design of hybrid DNA promoter elements have resulted in a toolkit for tunable and orthogonal regulation of gene expression in Arabidopsis thaliana and Nicotianabenthamiana plants.
Biosensors of guanine exchange factors (GEFs) and red-shifted GTPase biosensors are used to visualize GEF and GTPase activities in the same cells and enable correlation analysis to reveal which GEF–GTPase interactions regulate cell movement.
Evolution of a group of plant cellulose synthase-like enzymes into specialized glycosyltransferases in the endoplasmic reticulum membrane confers the ability to glucuronidate triterpenoid saponins and other specialized metabolites.
Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.
Structures of 5-lipoxygenase (5-LOX) reveal that NDGA disturbs regions that shield the active site while AKBA binds an allosteric site. NDGA inhibits 5-LOX activity using its redox-active function, while AKBA changes the enzyme’s regiospecificity
An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.
Structural and smFRET analysis reveals the mechanism of opposing catalytic activities of bifunctional Rel enzymes; that is, activation of one of the catalytic domains leads to allosteric inactivation of the other.
Lipidomics across the bilayer membrane plus biophysical and fluorescence approaches find asymmetry in phospholipid unsaturation and localization of protein transmembrane domains based on their ability to pack within the different membrane leaflets.
Development of BRET sensors for nearly all major G proteins show that GPCR–G-protein coupling ranges from promiscuous to extremely specific, Switch III is a novel site for G-protein engineering, and optimal donor–acceptor positioning is non-obvious.
Structures of the ketosynthase–chain length factor complex from ishigamide biosynthesis, cross-linked to the acyl carrier protein, reveal the molecular interactions between these domains and how the reaction pocket limits rounds of product extension.
The authors developed a metabolic labeling method via incorporation of allyl-SAM analogs to profile transcriptome-wide m6A at base resolution, which enables identification of m6A motifs and clustered m6A sites.
An antibody-independent m6A profiling method called m6A-SEAL was developed via turning m6A into stable dm6A after treatment by FTO and DTT. This method exhibits better reliability in detection of transcriptome-wide m6A sites in humans and plants.
Domain insertion into the loop region of AcrIIC1 leads to a variant with enhanced inhibitory activity toward Neisseria meningitides Cas9, while structure-guided design turns AcrIIC1 into a potent inhibitor of Staphylococcus aureus Cas9.
In plants, the cytosolic phenylalanine biosynthetic intermediate phenylpyruvate can serve as an amino acceptor in tryptophan-dependent auxin biosynthesis, thus facilitating crosstalk between these two distinct primary metabolic pathways.